N-lysine methyltransferase SETD8; H4-K20-HMTase SETD8; histone-lysine N-methyltransferase SETD8; lysine N-methyltransferase 5A; PR/SET domain-containing protein 07; PR-Set7; PR/SET07; SET domain-containing protein 8 (SETD8, KMT5A, PRSET7, SET07, SET8)
Jump to navigation
Jump to search
Function
- protein-lysine N-methyltransferase
- monomethylates both histones & non-histone proteins
- specifically monomethylates Lys-20 of histone H4 (H4K20me1)
- H4K20me1 is enriched during mitosis & represents a specific tag for epigenetic transcriptional repression
- mainly functions in euchromatin regions, thus playing a role in silencing of euchromatic genes
- required for cell proliferation, probably by contributing to maintenance of proper higher order structure of DNA during mitosis
- involved in chromosome condensation & proper cytokinesis
- nucleosomes are preferred as substrate compared to free histones
- mediates monomethylation of p53/TP53 at Lys-382, leading to repress p53/TP53-target genes
- interacts with L3MBTL1
- inhibition of SETD8 alone is sufficient to trigger replicative senescence in fibroblasts[2]
S-adenosyl-L-methionine + L-lysine-[[[A137031|histone]]] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[[[A137031|histone]]]
Structure
- although the SET domain contains the active site, both sequences upstream & downstream of the SET domain are required for methyltransferase activity
- belongs to the histone-lysine methyltransferase family, PR/SET subfamily
- contains 1 SET domain
Compartment
- nucleus, chromosome
- specifically localizes to mitotic chromosomes
- associates with silent chromatin on euchromatic arms
- not associated with constitutive heterochromatin
Alternative splicing
named isoforms=2
Expression
- not detected during G1 phase
- first detected during S through G2 phases, & peaks during mitosis (at protein level)
- induced by HCFC1 C-terminal chain, independently of HCFC1 N- terminal chain
- SETD8 decreases markedly in senescent fibroblasts[2]
Notes
More general terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/Q9NQR1.html
- ↑ 2.0 2.1 2.2 Kumamoto University Cellular senescence prevented by the SETD8 enzyme Science Daily. March 8, 2017 https://www.sciencedaily.com/releases/2017/03/170308092443.htm
Tanaka H, Takebayashi S, Sakamoto A et al The SETD8/PR-Set7 Methyltransferase Functions as a Barrier to Prevent Senescence-Associated Metabolic Remodeling. Cell Reports, 2017; 18 (9): 2148 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28249161 Free Article